112 



bution of mutations, judging by the 

 frequency with which single mutant 

 lethals were found in the same experi- 

 ments. Ordinarilv% then, the event that 

 causes the mutation is specific, affect- 

 ing just one particular kind of gene 

 of all the thousands present in the cell. 

 That this specificity is due to a spatial 

 limitation rather than a chemical one 

 is shown by the fact that when the 

 single gene changes the other one, of 

 identical composition, located near by 

 in the homologous chromosome of the 

 same cell, remains unaffected. This has 

 been proved by Emerson in corn, by 

 Blakeslee in Portulaca, and I have 

 shown there is strong evidence for it 

 in Drosophila. Hence these mutations 

 are not caused by some general perva- 

 sive influence, but are due to "acci- 

 dents" occurring on a molecular scale. 

 When the molecular or atomic mo- 

 tions chance to take a particular form, 

 to which the gene is vulnerable, then 

 the mutation occurs. 



It will even be possible to determine 

 whether the entire gene changes at 

 once, or whether the gene consists of 

 several molecules or particles, one of 

 which may change at a time. This 

 point can be settled in organisms hav- 

 ing determinate cleavage, by studies 

 of the distribution of the mutant char- 

 acter in somatically mosaic mutants. 

 If there is a group of particles in the 

 gene, then when one particle changes 

 it will be distributed irregularly 

 among the descendant cells, owing to 

 the random orientation of the two 

 halves of the chromosome on the 

 mitotic spindles of succeeding divi- 

 sions,* but if there is only one particle 



4 This depends on the assumption that if 

 the gene does consist of several particles, the 

 halves of the chromosomes, at each division, 

 receive a random sample of these particles. 

 That is almost a necessary assumption, since 

 a gene formed of particles each one of which 

 was separately partitioned at division would 



MULLER 



to change, its mutation must affect all 

 of the cells in a bloc, that are de- 

 scended from the mutant cell. 



(c) The Co?iditions mider which 

 the Change occurs 



But the method that appears to have 

 most scope and promise is the experi- 

 mental one of investigating the condi- 

 tions under which mutations occur. 

 This requires studies of mutation fre- 

 quency under various methods of 

 handling the organisms. As yet, ex- 

 tremely little has been done along this 

 line. That is because, in the past, a 

 mutation was considered a windfall, 

 and the expression "mutation fre- 

 quency" would have seemed a con- 

 tradiction in terms. To attempt to 

 study it would have seemed as absurd 

 as to study the conditions affecting 

 the distribution of dollar bills on the 

 sidewalk. You were simply fortunate if 

 you found one. Not even controls, 

 giving the "normal" rate of mutation— 

 if indeed there is such a thing— were 

 attempted.''^ Of late, however, we may 

 say that certain verv^ exceptional bank- 

 ing houses have been found, in front 

 of which the dollars fall more fre- 

 quently—in other words, specially mu- 

 table genes have been discovered, that 

 are beginning to yield abundant data 

 at the hands of Nilsson-Ehle, Zeleny, 

 Emerson, Anderson and others. For 

 some of these mutable genes the rate 

 of change is found to be so rapid that 

 at the end of a few decades half of 



tend not to persist as such, for the occur- 

 rence of mutation in one particle after the 

 other would in time differentiate the gene 

 into a number of different genes consisting 

 of one particle each. 



5 Studies of "mutation frequency" had of 

 course been made in the CEnotheras, but as 

 we now know that these were not studies of 

 the rate of gene change but of the fre- 

 quencies of crossing over and of chromo- 

 some aberrations they may be neglected for 

 our present purposes. 



